Granulocyte colony-stimulating factor (G-CSF) has a molecular weight of approximately 18,000 to 22,000 and consists of 174 (in rare cases 178) amino acids in the case of humans and 178 amino acids in the case of mice. It is a glycoprotein that induces differentiation and proliferation of neutrophils, one of the types of leukocytes.
G-CSF has a potential of survival-extension and functional promotion to the mature neutrophils, and also has ability to form erythroblasts in response to erythropoietin and blast cell colonies in response to interleukin-3. Cells that produce G-CSF are macrophages, stroma cells, monocytes, T lymphocytes, fibroblasts, vascular endothelial cells and so forth.
Administration of G-CSF drug exhibits a therapeutic effect on neutropenia induced by side effect of anticancer agents, or neutropenia following bone marrow transplantation, and a therapeutic effect on anaplastic anemia. Because of its low stability in the blood, however, it requires frequent administration, and because its administration is limited to the intravenous route, this has resulted in a great deal of pain and burden to the patient and physician. Furthermore, administration of G-CSF as a drug has been reported to cause ostalgia as a side-effect. The alternative option of direct administration of macrophages or stroma cells that produce G-CSF will produce the risk of unknown side-effects since the cells contain numerous proteins and other substances, and therefore such treatment has not been practiced.
Because administration of G-CSF itself for differentiation and proliferation of neutrophils provoke ostalgia as a side-effect, and it also requires frequent administration and increases the pain and burden to the patient and physician, it has been strongly desired to develop an alternative treatment method; however, no such method has yet been established.
With the intent of causing production of G-CSF and differentiation and proliferation of neutrophils without administration of G-CSF itself, the present inventors have already succeeded in providing G-CSF inducing antibodies (Japanese Patent Application HEI No. 9-266591 (Sep. 30, 1997), Japanese Unexamined Patent Publication HEI No. 11-106400 (Apr. 20, 1999)).
However, the antigens recognized by the G-CSF inducing antibodies have not yet been discovered.
One problem to be solved by the present invention, therefore, is to identify an antigen recognized by G-CSF inducing antibodies. Another problem to be solved by the invention is to clone and identify the gene encoding the antigen recognized by the G-CSF inducing antibodies.